It has been assumed for some time that the primary source of the antitumor activity of the fluorinated pyrimidines is the inhibition of the antitumor activity of the fluorinated pyrimidines is the inhibition of thymidylate synthetase and the subsequent inhibition of DNA synthesis. However, several of these compounds are known to be potent inhibitors of ribosomal RNA maturation in both procarvotes and eucarvotes. Since the syntesis of ribosomes during the G1 phase of the cell cycle is a prerequisite for DNA synthesis during the S phase, the inhibition of ribosomal RNA maturation by the fluorinated pyrimidines may be of equal, or even greater, importance than the inhibition of DNA synthesis. The objective of the proposed research is to determine the relative importance of the inhibition of ribosomal RNA maturation in the overall cytotoxic activity of 5-fluorouridine, 5-fluorouracil in Novikoff hepatoma cells. This will be accomplished by treating cells with these drugs under various experimental conditions and following simultaneously cell growth, ribosomal RNA maturationm and DNA synthesis. The information obtained could provide new insights for the design of more effective therapeutic regimens or combination drug therapy. Knowledge of the exact sites of inhibition and the cell cycle specificity will help clinicians take full advantange of cytotoxic potential of these drugs. BIBLIOGRAPHIC REFERENCES: WILKINSON, D. S., T.D. Tlsty and R. J. Hanas (1975). The inhibition of Ribosomal RNA Synthesis and Maturation in Novikoff Hepatoma Cells by 5-Fluorouridine. Cancer Research 35, 3014-3020. Wilkinson, D.S. and L.D. Prockup (1976). Hypoglycemia: Effect on the Central Nervous System. Vienken, P.J., and Bruyn, G.W., eds. Handbook of Clinical Neurology, Vo. 29, Amsterdam, North-Holland Publishing Company. In press.